Automated system and method for processing genetic material

ABSTRACT

The invention discloses an automated system and method for processing genetic material. Additionally, the automated system and method of the invention can extract a target genetic material from a sample; amplifying a target nucleic acid sequence from the genetic material; detecting the target nucleic acid by an optical detection module to qualify and/or quantify the target nucleic acid immediately.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to an automated system andmethod for processing genetic materials, and more particularly, to asystem and method for automatically extracting and amplifying geneticmaterials.

2. Description of the Prior Art

Genome sequencing and decoding of several organisms have recently beenperformed in many research institutes. With the understanding of thesequence, function, structure, and other characteristics of geneticmaterial, such as nucleic acids (e.g. deoxyribonucleic acid (DNA) orribonucleic acid (RNA)), the detection methods based on said geneticmaterial are widely developed. Generally speaking, said detectionmethods are used to detect specific nucleic acid sequences or amino acidsequences in samples such as blood, tissue fluid, and cell culturesolution.

In the prior art, the detection method comprises several steps to detectthe presence of a specific nucleic acid sequence in a sample, or toquantify the specific nucleic acid sequence in the sample. Particularly,the method can further be used to speculate the presence of specificorganisms, such as bacteria, fungus, virus, and a number of saidspecific organisms.

Before the detection, we have to extract the nucleic acid sequence fromthe sample and perform polymerase chain reaction (PCR) with specificprobes to amplify the target nucleic acid sequence.

However, the complex processes of the above-mentioned extraction andanalysis will increase the possibility of artificial error and bias.Moreover, the time needed by the processes could be very long and theaccuracy of analysis would be affected.

SUMMARY OF THE INVENTION

Accordingly, a scope of the present invention is to provide an automatedsystem and method for processing genetic material to solve the problemsof the prior art.

According to a preferred embodiment, the automated system for processinggenetic material of the invention includes a platform, a pipettingmodule, an extracting module, a temperature-control module, an opticaldetection module, and a processing module.

Furthermore, the platform includes a first set of receptacles, each ofwhich is capable of containing a sample, and the pipetting modulecomprises at least a pipet for sucking and moving at least a firstreagent to the first set of receptacles. Additionally, the extractingmodule is applied to cooperate with the first reagent to extract atarget genetic material from the sample. The temperature-control moduleis used for providing a plurality of thermal cycles and cooperating withat least a second reagent to amplify a target nucleic acid sequence ofthe target genetic material. The optical detection module is applied fordetecting the presence of the target nucleic acid sequence, andgenerating a detecting signal. The processing module can receive thedetecting signal, and it can also qualify and/or quantify the targetnucleic acid sequence. Particularly, in an embodiment, the opticaldetection module can detect the presence, the quantity, or the qualityof the target nucleic acid sequence during amplification.

According to another preferred embodiment, the automated method forprocessing genetic material comprises the automated steps of: (a) mixinga sample with at least a first reagent to extract a target geneticmaterial from the sample; (b) mixing the target genetic material with atleast a second reagent; (c) providing a plurality of thermal cycles toamplify a target nucleic acid sequence of the target genetic material;(d) detecting the presence of the target nucleic acid sequence andgenerating a detecting signal; and (e) receiving the detecting signaland qualifying and/or quantifying the target nucleic acid sequence.Particularly, in an embodiment, step (c) to step (e) can be optionallyperformed either simultaneously or sequentially.

The objective of the present invention will no doubt become obvious tothose of ordinary skill in the art after reading the following detaileddescription of the preferred embodiment, which is illustrated in thevarious figures and drawings.

BRIEF DESCRIPTION OF THE APPENDED DRAWINGS

FIG. 1 illustrates the automated system for processing genetic materialof an embodiment of the invention.

FIG. 2 illustrates the side view of the automated system for processinggenetic material in FIG. 1.

FIG. 3 illustrates the front view of the automated system for processinggenetic material in FIG. 1.

FIG. 4A to 4F illustrate the automated method for processing geneticmaterial of an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides an automated system and method for processinggenetic material. Reference will now be made in detail to the presentpreferred embodiments of the invention, examples of which areillustrated in the accompanying drawings. Wherever possible, the samereference numbers are used in the drawings and the description to referto the same or like parts.

According to an embodiment of the invention, the automated system forprocessing genetic material can include a platform, a pipetting module,an extracting module, a temperature-control module, an optical detectionmodule, and a processing module.

The platform includes a first set of receptacles, and each of thereceptacles can contain a sample. In practice, the sample can be anysuitable liquid, solid or living sample. The liquid sample can be, butnot limited to, blood, saliva, tissue fluid, cell culture solution,microorganism culture solution, and other suitable liquid samples; thesolid sample can be, but not limited to, tissue slide, organ slide, andother suitable solid samples; and the living sample can be, but notlimited to, nematode (e.g. Caenorhabditis elegans), fish eggs, embryo,and other suitable living samples.

The pipetting module includes at least a pipet, for sucking and movingat least a first reagent to the first set of receptacles. In practice,the pipetting module can be performed in the form of robotic pipettor.Moreover, in practice, the pipetting module includes a plurality ofpipets with different scales.

The extracting module can cooperate with the first reagent to extract atarget genetic material from the sample. Practically, the first reagentcan be, but not limited to, PK solution, cell lysis buffer, wash buffer,elution buffer, magnetic particle solution, and other suitable reagents.Particularly, in practice, the above-mentioned magnetic particlesolution contains many magnetic particles, and the surface of themagnetic particles can be coated with nucleic acid absorbing material(e.g. silicon) to absorb nucleic acids. Furthermore, the pH value andthe ion concentration of the magnetic particle solution can be suitablyadjusted to regulate the absorbing strength between the magneticparticles and the nucleic acids.

The temperature-control module can provide settings of differenttemperature to the above-mentioned platform and/or the extracting moduleto assist the extraction. Furthermore, the temperature-control modulecan further provide a plurality of thermal cycles and cooperates with atleast a second reagent to amplify a target nucleic acid sequence of thetarget genetic material.

The optical detection module can detect the presence of theabove-mentioned target nucleic acid sequence, and further detects thequality or quantity of the target nucleic acid sequence. Particularly,the optical detection module can simultaneously perform the detectionwhen the temperature-control module provides the thermal cycles, orafter the temperature-control module provides the thermal cycles.

The processing module, such as a micro-control unit (MCU) or centralcontrol unit (CPU), is connected to the optical detection module, forreceiving the detecting signal, and qualifying and/or quantifying thetarget nucleic acid sequence in accordance with the detecting signal.

Please refer to FIG. 1 to FIG. 3. FIG. 1 illustrates an automated systemfor processing genetic material of an embodiment of the invention; FIG.2 illustrates the side view of the automated system in FIG. 1; and FIG.3 illustrates the front view of the automated system in FIG. 1. In theembodiment, the automated system 3 for the processing of geneticmaterial includes a housing 30, a platform 31, a pipetting module 32, anextracting module 33, a temperature-control module 34, an opticaldetection module 35, a pipet tip container 36, a reagent container 37, aPCR reaction module 38, and a waste-discarding region 39.

In the embodiment, a first set of receptacles 312, a second set ofreceptacles 314, and a third set of receptacles 316 are disposed on theplatform 31. In practice, the first set of receptacles 312 can be formedof a non-magnetic material with high thermal conductivity (such as, butnot limited to, aluminum and silver). The first set of receptacles 312can contain a plurality of eppendorf tubes 40, and each of the eppendorftubes 40 can contain a sample. In practice, the second set ofreceptacles 314 can be formed of a non-magnetic material with lowthermal conductivity (such as, but not limited to, acrylic material).The second set of receptacles 314 can also contain a plurality ofeppendorf tubes 40, and each of the eppendorf tubes 40 can contain thetarget genetic material extracted from the sample. In practice, thethird set of receptacles 316 can be formed of a non-magnetic materialwith high thermal conductivity (such as, but not limited to, aluminumand silver). The third set of receptacles 316 can also contain aplurality of eppendorf tubes 40, and each of the eppendorf tubes 40 cancontain the mixture of the target genetic material and second reagent.

The pipet tip container 36 contains a plurality of tips 362 which eachhas a scale (e.g. 10 μl, 20 μl, 50 μl, 100 μl, 200 μl, 500 μl, 1000 μl,or optionally other scales). The reagent container 37 comprises aplurality of reagent receptacles 372 for containing the first reagentand/or the second reagent.

Additionally, the pipetting module 32 includes several pipets 324 withdifferent ranges of scale. Moreover, the pipetting module 32 can beconnected to the moving module 320, so that the moving module 320 canhorizontally or vertically move the pipetting module and positioning thepipetting module 32. Accordingly, the pipetting module 32 canselectively use one of the pipets 324 to wedge suitable tip 362 on thepipet tip container 36 to suck and/or move the sample and the reagent inthe reagent receptacles 372.

Particularly, all of the above-mentioned first set of receptacles 312,second set of receptacles 314, and third set of receptacles 316 can bedesigned to be removable. Furthermore, part of the first reagents can beadded in the eppendorf tubes 40 of the first set of receptacles 312 inadvance, and part or all of the second reagents can be added in theeppendorf tubes 40 of the third set of receptacles 316 in advance, so asto reduce the moving frequency of the pipetting module 32 and theoperation time of the system of the invention.

In the embodiment, the temperature-control module 34 is disposed betweenthe platform 31 and the sets of receptacles 312, 314 and 316, to providesuitable temperature to the sets of receptacles 312, 314 and 316.Furthermore, the moving module 318 can be connected to the platform 31,so as to horizontally or vertically move the platform 31 and positionthe platform 31.

As shown in FIG. 1 and FIG. 2, the extracting module 33 in theembodiment is rotatably mounted adjacent to the platform 31, so that theextracting module 33 is optionally disposed close to the first set ofreceptacles 312. Particularly, when the first reagent includes amagnetic particle solution, the extracting module 33 (e.g. comprisesstrong permanent magnet) can generate a magnetic field adjacent to thefirst set of receptacles 312 after the mixture of the sample and thefirst reagent in the first set of receptacles 312. The magnetic fieldcan fix the magnetic particles with the target nucleic acid on the innerwall of the first set of receptacles 312. At that time, the pipettingmodule 32 can remove residues other than the magnetic particles to reachthe goal of isolating the target nucleic acid from the sample.

The PCR reaction module 38 includes a reaction chamber 382 and a door380 of the reaction chamber 382. The reaction chamber 382 can containthe third set of receptacles 316 which comprises eppendorf tubes 40containing the second reagent and the target genetic material. The door380 can be disposed closest to the opening of the reaction chamber 382,so as to seal the second reagent and the target genetic material in thereaction chamber 382. Moreover, the PCR reaction module 38 receives thethermal cycles provided by the temperature-control module 34 to amplifythe target nucleic acid sequence.

When the above-mentioned PCR reaction module 38 performs theamplification process, the optical detection module 35 can performoptical detection of the eppendorf tubes 40 on the third set ofreceptacles 316, so as to immediately detect the presence of the targetnucleic acid sequence. As mentioned above, the optical detection module35 can perform optical detection after the amplification processes.Particularly, in practice, the optical detection module 35 has a specialstructure to assist the PCR reaction module 38 to seal the mixture ofthe second reagent and the target genetic material in the reactionchamber 382. Moreover, the heating mechanism of the optical detectionmodule 35 can prevent the steam from congealing on the inner wall of theeppendorf tubes 40 of the third set of receptacles 316 or evaporating.Furthermore, the waste-discarding region 39 can contain the wastedmaterial or liquid discarded by the pipetting module 32.

Please refer to FIG. 4A to 4F which illustrate the automated steps forprocessing genetic material of an embodiment of the invention. In theembodiment, the sample has been added in the eppendorf tubes 40 of thefirst set of receptacles 312.

First of all, as shown in FIG. 4A, the moving module 320 horizontallymoves the pipetting module 32 to the top of the pipet tip container 36,and vertically moves the pipet 324 with suitable scale of the pipettingmodule 32 to wedge the tip 362 matching with the pipet 324. Afterward,as shown in FIG. 4B, the moving module 320 horizontally moves thepipetting module 32 to the top of the reagent container 37, and thenvertically moves the above-mentioned pipet 324 with the tip 362 to letthe pipetting module 32 suck suitable volume of PK solution.

Consequently, as shown in FIG. 4C, the moving module 320 horizontallymoves the pipetting module 32 to the top of the eppendorf tubes 40 ofthe first set of receptacles 312, and then vertically moves theabove-mentioned pipet 324, so that the tip 362 wedged thereon can bemoved close to the eppendorf tubes 40. At that time, the pipettingmodule 32 adds the PK solution to the eppendorf tubes 40, and mixes thePK solution and the sample. Furthermore, as shown in FIG. 4D, the movingmodule 320 horizontally moves the pipetting module 32 to the top of thewaste-discarding region 39, and the pipetting module 32 discards theused tip 362 to the waste-discarding region 39.

By the similar processes as mentioned above, the pipetting module 32further adds suitable volume of cell lysis buffer in the eppendorf tubes40 of the first set of receptacles 312 and mixes the cell lysis bufferwith the PK solution and the sample. Furthermore, thetemperature-control module 34 can optionally heat the first set ofreceptacles 312 to assist the cell in the sample to be lysed. Thepipetting module 32 further adds suitable volume of magnetic particlesolution in the eppendorf tubes 40 of the first set of receptacles 312,so that the target genetic material can be adhered on the surface ofmagnetic particles. Afterward, as shown in FIG. 4E, the extractingmodule 33 rotates to be close to the first set of receptacles 312, andenforces a magnetic field to the first set of receptacles 312, so thatthe magnetic particles with the target genetic material attached on theinner wall of the eppendorf tubes 40. Afterward, the extracting module33 maintains the position in FIG. 4E, and the pipetting module 32removes residues other than the magnetic particles to thewaste-discarding region 39.

Consequently, the extracting module 33 rotates to the position as shownin FIG. 4D, and the pipetting module 32 adds wash buffer in theabove-mentioned eppendorf tubes 40 to wash the magnetic particles.Afterward, the extracting module 33 rotates to be moved close to thefirst set of receptacles 312 and enforces magnetic field again, andallows the magnetic particles with the target genetic material beattached on the inner wall of the eppendorf tubes 40. Again, thepipetting module 32 removes residues other than the magnetic particlesto the waste-discarding region 39. Please note that the above-mentionedwash process can be optionally performed several times.

Consequently, the extracting module 33 rotates to the position as shownin FIG. 4D, and the pipetting module 32 adds elution buffer in theabove-mentioned eppendorf tubes 40 to elute the target genetic materialfrom the magnetic particles. Afterward, the extracting module 33 rotatesto be moved close to the first set of receptacles 312 and enforces themagnetic field again, and allows the magnetic particles to be attachedon the inner wall of the eppendorf tubes 40. At that time, the pipettingmodule 32 sucks the eluted target genetic material and moves it to theeppenforf tubes 40 of the second set of receptacles 314.

Consequently, the pipetting module 32 moves suitable volume of targetgenetic material from the eppendorf tubes 40 of the second set ofreceptacles 314 to the eppendorf tubes 40 (already contained secondreagent) of the third set of receptacles 316. Finally, as shown in FIG.4F, the moving module 318 moves the platform 31 to allow the third setof receptacles 316 enter the reaction chamber 382 and the door 380 isdisposed close to the opening of the reaction chamber 382. Then, thetemperature-control module 34 provides pre-set thermal cycles (e.g. 95°C.-54° C.-72° C.) to amplify the target nucleic acid sequence of thetarget genetic material. As mentioned above, the optical detectionmodule 35 can detect the presence of the target nucleic acid sequencesimultaneously or after the amplification, and the result of thedetection can be used to qualify and/or quantify the target nucleic acidsequence.

Practically, the automated system for processing genetic material canoptionally provide a vacuum environment, a germfree environment, anegative pressure environment or other suitable environment to performthe above-mentioned experiments, so as to prevent the error caused byenvironment factors. It should be noted that the automated system of theinvention can optionally include other suitable modules or members andthe design and disposition of said modules or members can optionally beadjusted, but not limited to, the above-mentioned embodiments.

To sum up, the automated system and method for processing geneticmaterial of the invention can extract the genetic material and amplifythe nucleic acid sequence with completely automatic processes.Accordingly, the system and method of the invention can simplify therelated processes of the prior art, and can reduce the error and biasgenerated by artificial operation. Additionally, the automated system ofthe invention can process sets of samples simultaneously, so as toreduce the operation time.

Although the present invention has been illustrated and described withreference to the preferred embodiment thereof, it should be understoodthat it is in no way limited to the details of such embodiment but iscapable of numerous modifications within the scope of the appendedclaims.

1. An automated system for processing genetic material, comprising: aplatform comprising a first set of receptacles, each of which is capableof containing a sample; a pipetting module comprising at least a pipet,for moving at least a first reagent to the first set of receptacles; anextracting module, for cooperating with the first reagent to extract atarget genetic material from the sample; a temperature-control module,for providing a plurality of thermal cycles and cooperating with atleast a second reagent to amplify a target nucleic acid sequence of thetarget genetic material; an optical detection module, for detecting thepresence of the target nucleic acid sequence, and generating a detectingsignal; and a processing module, for receiving the detecting signal, andqualifying and/or quantifying the target nucleic acid sequence.
 2. Theautomated system for processing genetic material of claim 1, furthercomprising: a housing containing the platform, the pipetting module, theextracting module, the temperature-control module, and the opticaldetection module.
 3. The automated system for processing geneticmaterial of claim 1, further comprising: a pipet tip containercontaining a plurality of tips which each has a scale, wherein thepipetting module selects one of the tips to suck or to move the sample,the first reagent, and the second reagent.
 4. The automated system forprocessing genetic material of claim 1, further comprising: a reagentcontainer comprising a plurality of reagent receptacles for containingthe first reagent and/or the second reagent.
 5. The automated system forprocessing genetic material of claim 1, further comprising: a firstmoving module, connected to the pipetting module, for horizontally orvertically moving the pipetting module and positioning the pipettingmodule.
 6. The automated system for processing genetic material of claim1, further comprising: a second moving module connected to the platformfor horizontally moving the platform and positioning the platform. 7.The automated system for processing genetic material of claim 1, furthercomprising: a PCR reaction module, disposed adjacent to thetemperature-control module and the optical detection module, for sealingthe second reagent and the target genetic material, and for receivingthe thermal cycles to amplify the target nucleic acid sequence, and theoptical detection module being capable of immediately detecting thepresence of the target nucleic acid sequence.
 8. The automated systemfor processing genetic material of claim 1, further comprising: awaste-discarding region, for containing a waste material or a liquidwaste.
 9. The automated system for processing genetic material of claim1, further comprising: a second set of receptacles, for containing thetarget genetic material; and a third set of receptacles, for containingthe target genetic material and the second reagent.
 10. The automatedsystem for processing genetic material of claim 9, wherein the secondset of receptacles is formed of a non-magnetic material with low thermalconductivity.
 11. The automated system for processing genetic materialof claim 9, wherein the third set of receptacles is formed of anon-magnetic material with high thermal conductivity.
 12. The automatedsystem for processing genetic material of claim 9, wherein the secondreagent is added in the third set of receptacles in advance.
 13. Theautomated system for processing genetic material of claim 1, wherein thefirst set of receptacles is formed of a non-magnetic material with highthermal conductivity.
 14. The automated system for processing geneticmaterial of claim 1, wherein the extracting module is capable ofgenerating a magnetic field.
 15. The automated system for processinggenetic material of claim 1, wherein the extracting module is rotatablymounted adjacent to the platform, and the extracting module beingoptionally disposed close to the first set of receptacles.
 16. Theautomated system for processing genetic material of claim 1, wherein thefirst reagent is selected from a group consisting of PK solution, celllysis buffer, wash buffer, elution buffer and magnetic particlesolution.
 17. An automated method for processing genetic material,comprising the following steps of: (a) mixing a sample with at least afirst reagent to extract a target genetic material from the sample; (b)mixing the target genetic material with at least a second reagent; (c)providing a plurality of thermal cycles to amplify a target nucleic acidsequence of the target genetic material; (d) detecting the presence ofthe target nucleic acid sequence and generating a detecting signal; and(e) receiving the detecting signal and qualifying and/or quantifying thetarget nucleic acid sequence.
 18. The automated method for processinggenetic material of claim 17, wherein step (a) further comprises thefollowing step: (a1) mixing the sample and the first reagent to form amixed solution and selectively enforcing a magnetic field to the mixedsolution to isolate the target genetic material from the sample.
 19. Theautomated method for processing genetic material of claim 17, whereinthe sample and the first reagent in step (a) and the target geneticmaterial and the second reagent in step (b) are mixed via a pipettingmodule.
 20. The automated method for processing genetic material ofclaim 17, wherein step (c) is performed in a PCR reaction module. 21.The automated method for processing genetic material of claim 17,wherein step (d) is performed by an optical module.
 22. The automatedmethod for processing genetic material of claim 17, wherein step (e) isperformed by a processing module.
 23. The automated method forprocessing genetic material of claim 17, wherein step (c) to step (e)are performed simultaneously or sequentially.
 24. The automated methodfor processing genetic material of claim 17, wherein the first reagentis selected from a group consisting of PK solution, cell lysis buffer,wash buffer, elution buffer and magnetic particle solution.